Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and progressive bone destruction. Its pathological core lies in the aberrant activation of fibroblast-like synoviocytes (FLS) and involves a cascade of pyroptosis mediated by the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. This article systematically reviews the pathological patterns of inflammatory bone destruction in RA, with a particular focus on the role of exosomes derived from mesenchymal stem cells (MSC-Exo) in carrying microRNAs (miRNAs). These miRNAs can regulate the NLRP3 inflammasome signaling axis and play a crucial role in inhibiting FLS pyroptosis. This article provides a new perspective for RA treatment by regulating exosome miRNA to intervene in cell pyroptosis. However, the specific molecular targets, clinical translational value, and functional synergism among different non-coding RNAs (ncRNAs) still need further validation.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized primarily by joint destruction. Anti-citrullinated protein antibodies (ACPA) are not only key drivers and major risk factors for the onset and immune persistence of RA but also crucial biomarkers for its clinical diagnosis. Recent studies have demonstrated that ACPA can directly exacerbate the clinical symptoms of RA through various mechanisms, including promoting inflammatory responses, mediating bone erosion, and inducing pain. Therefore, ACPA holds significant value not only for the early diagnosis, prognosis assessment, and treatment monitoring of RA but is also regarded as a highly promising therapeutic target, offering new directions for developing precision treatment strategies for RA. This article reviews the latest research progress on the correlation between ACPA and the core clinical symptoms as well as common complications of RA, aiming to provide a theoretical basis for a deeper understanding of the pathogenesis and the development of personalized treatment plans for ACPA-positive RA patients.

Reductions in musculoskeletal mass and function can occur with ageing and disuse. While resistance exercise training is known to minimise these detriments, it is not always feasible. Vortex wave stimulation (VWS) may mitigate skeletal muscle decline in such scenarios. The aim of the present study was to explore the acute physiological and metabolic effects of VWS in healthy older adults. Fourteen participants consumed deuterium oxide (D2O) stable oral isotope tracer for 7 days. Serial skeletal muscle biopsies were obtained to measure integrated rates of myofibrillar (iMyoPS) and sarcoplasmic (iSarcPS) muscle protein synthesis and regulatory signalling over ∼48 h before (habitual) and after two consecutive-day bouts of VWS. Myoelectrical activity and muscle oxygenation during VWS, and pre-post changes in peripheral blood flow and concentrations of inflammatory and bone turnover markers were also measured. There was an increase in iMyoPS (0.23% day-1, P = 0.025), but not iSarcPS (0.07% day-1, P = 0.582) above habitual rates following VWS. There was no difference in the expression of anabolic signalling proteins, nor peripheral blood flow following VWS. Myoelectrical activity increased during VWS (9.47 µV, P = 0.010), while muscle oxygenation decreased at the gastrocnemius (P = 0.001) and quadriceps (P = 0.017). There was a reduction in P1NP (8.27 µg L-1) and lactate (0.84 mmol L-1) concentration post-VWS (both P < 0.001), while there was no difference in other biomarkers. This is the first study to demonstrate that VWS elicits acute physiological responses congruent with musculoskeletal adaptive remodelling, which warrants further exploration. KEY POINTS: Resistance exercise is known to mitigate skeletal muscle atrophy associated with ageing and/or disuse but is not always feasible. We investigated, for the first time, the effects of a novel mechanical stimulus - vortex wave stimulation (VWS) - on integrated rates of myofibrillar and sarcoplasmic muscle protein synthesis, alongside other musculoskeletal and physiological outcomes, in healthy older adults. We demonstrated that VWS elevated myofibrillar, but not sarcoplasmic muscle protein synthesis compared to baseline, while increasing myoelectrical activity and reducing muscle oxygen saturation, lactate and bone turnover markers. These findings suggest VWS elicits acute physiological responses congruent with musculoskeletal adaptive remodelling.

Osteosclerosis refers to an abnormal increase in bone density resulting from excessive bone formation and/or reduced bone resorption. We present a case of a 31-year-old woman with acute-on-chronic abdominal pain, flushing, and diarrhea. Diffuse, mottled sclerosis involving the entire axial and appendicular skeleton was incidentally identified on imaging. Diagnostic investigations for osteosclerosis revealed a raised tryptase, leading to a bone marrow and trephine analysis. This demonstrated abnormally spindle-shaped mast cells, more than 15 in a group, with positive staining for tryptase which was consistent with systemic mastocytosis (SM). In the absence of "C" findings, a diagnosis of indolent SM complicated by diffuse osteosclerosis was made. Treatment with a histamine type-2 receptor antagonist provided mild symptomatic relief. In this report, we discuss the differential causes of osteosclerosis and the pathogenesis of bone manifestations related to SM, along with subtype-specific SM treatment options.

Temporomandibular joint ankylosis (TMJa) is an incapacitating disease due to the fusion of the mandibular condyle with the temporal bone, leading to restricted mouth opening. In children, early surgical intervention is required to avoid alterations in growth and irreversible facial deformity. This case report outlines the treatment of unilateral Type III bony TMJa with piezo-assisted gap arthroplasty and pedicled buccal fat pad interposition in a six-year-old female. We performed osteotomy with a piezoelectric surgical device to control bone resection and decrease the potential for injury to surrounding soft tissues and vital structures. Incision was made approximately 10 mm apart, and ipsilateral coronoidectomy of the mandible was performed to increase range of motion. Early physiotherapy was performed postoperatively to maintain functional mouth opening. The patient showed more than 20 mm mouth opening when followed up, with good functional recovery. The piezoelectric surgical technique offers an accurate, secure modern approach for the surgical management of TMJa compared to the conventional rotary instruments.

Glucocorticoids (GCs) affect the Wnt signaling pathway, which is a key mechanism underlying GC-induced osteoporosis (GIOP). The efficacy of romosozumab (ROMO), an antibody targeting sclerostin-an inhibitor of Wnt signaling-in treating GIOP remains unclear, as does its effectiveness when used sequentially after bisphosphonates (BP). In this prospective observational study, we aimed to evaluate the efficacy of ROMO as a sequential therapy following BP in patients with GIOP. Patients with rheumatic diseases receiving BP and GCs equivalent to 5 mg/d or more of prednisolone for at least 6 mo were enrolled and either switched from BP to ROMO (ROMO group) or continued on BP (BP group). BMD of the LS (L2-4), FN, and TH were measured every 6 mo, and bone turnover markers were assessed every 3 mo. Six patients in the ROMO group and 22 in the BP group were analyzed. Patients in the ROMO group were significantly older (78.5 vs 64.5 yr), had a higher history of vertebral fractures, had lower baseline BMD of the FN and TH, and tended to receive higher GC dose (8.0 mg vs 5.0 mg) compared with the BP group. The median (25th-75th percentile) BMD percent changes at 12 mo were numerically higher in the ROMO group compared to the BP group (LS 2.6 [0.8-3.4] % vs 1.6 [-1.9-4.3] %; FN 1.4 [-0.5-5.4] % vs 1.0 [-4.7-5.6] %; TH: 1.1 [-7.6-6.5] % vs -1.8 [-6.4-1.8] %), although their differences were not statistically significant. One new vertebral fracture was observed in the BP group, and 1 patient in the ROMO group experienced a cerebral infarction. These findings suggest that ROMO may be an effective sequential therapy for BP in patients with GIOP.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome in which a mesenchymal tumor secretes fibroblast growth factor 23 (FGF-23), causing renal phosphate wasting and osteomalacia. A 62-year-old woman was referred to our hospital with a two-year history of progressive muscle weakness and generalized bone pain. The patient was nonambulatory and required a wheelchair for mobility. Laboratory evaluation revealed hypophosphatemia and low serum 1,25-dihydroxyvitamin D levels. Further investigation of the hypophosphatemia demonstrated an elevated fractional excretion of phosphate (FeP) and increased serum FGF-23 levels. Genetic testing was negative. A 68Ga-DOTANOC PET/CT scan identified an infiltrative cervical lesion with increased somatostatin receptor expression. The tumor was surgically resected, after which the patient recovered functional ambulation, and serum phosphate normalized. One year later, the patient reported recurrence of musculoskeletal symptoms. Laboratory findings showed hypophosphatemia with an elevated FeP, raising suspicion of tumor recurrence. A repeat 68Ga-DOTANOC PET/CT scan demonstrated increased somatostatin receptor expression in a right parietal calvarial lesion that was not amenable to surgical resection or radiotherapy. Initiation of burosumab therapy led to the normalization of serum phosphate levels and complete resolution of symptoms. TIO is a rare disorder that is frequently misdiagnosed as osteoporosis, resulting in substantial diagnostic delay. A systematic evaluation of hypophosphatemia is essential for timely diagnosis and appropriate management. This case supports burosumab as an effective therapeutic option for achieving biochemical and clinical improvement in patients with unresectable TIO.

Chronic refractory pain in knee osteoarthritis (KOA) is among the leading causes of physical disability worldwide. While KOA is traditionally characterized by articular cartilage degradation, subchondral bone remodeling, synovial inflammation, and periarticular soft tissue lesions, the structural damage frequently dissociates from the symptomatic pain severity. Emerging neurobiological evidence suggests that central sensitization (CS)-the pathological neuroplastic remodeling of the central nociceptive networks-may play a pivotal role in the exacerbation and maintenance of KOA pain. Conventional therapeutic approaches primarily act on peripheral joints. Consequently, these approaches often yield suboptimal analgesic efficacy in patients who have already developed deep-rooted CS, while also carrying risks of potential side effects. Given these clinical challenges, neuromodulation has emerged as a potential alternative or adjunctive analgesic strategy. By directly manipulating neural activity to potentially reverse maladaptive plasticity, these modalities may provide a novel framework targeting CS structurally and functionally, potentially addressing the limitations of conventional medicine. Recent technological advancements have accelerated the exploration of both non-invasive techniques-including transcutaneous electrical nerve stimulation (TENS), transcranial direct current stimulation (tDCS), and repetitive transcranial magnetic stimulation (rTMS)-and invasive procedures, such as spinal cord stimulation (SCS) and dorsal root ganglion stimulation (DRGS). From the perspective of combating CS, this narrative review summarizes the mechanistic basis and clinical evidence of diverse neuromodulatory applications in KOA pain management. Furthermore, we propose the integration of Quantitative Sensory Testing (QST) for the phenotypic stratification of sensitization in patients, which may facilitate a paradigm shift toward precision neuromodulation in KOA.

We report the case of a man diagnosed with chronic-phase chronic myeloid leukemia (CML) at 24 years of age after marked leukocytosis was incidentally identified during routine blood donation screening. Initial evaluation demonstrated a white blood cell count of 187.8 ×10³/µL, anemia, basophilia, and left-shifted myeloid proliferation. Bone marrow examination confirmed chronic-phase CML, and cytogenetic analysis identified a rare variant Philadelphia chromosome translocation, t(6;9;22)(q34;q11.2;p21). Fluorescence in situ hybridization confirmed BCR::ABL1 rearrangement in 94.5% of analyzed cells. Nine years after diagnosis, the patient was hospitalized for evaluation of persistent disease. Repeat bone marrow examination demonstrated markedly hypercellular marrow (95% cellularity) with myeloid hyperplasia, decreased erythropoiesis, and moderate reticulin fibrosis (MF-2), without evidence of accelerated-phase or blast-phase transformation. Peripheral blood flow cytometry identified a small CD34-positive immature myeloid population (3.8-4.3% of leukocytes) without immunophenotypic evidence of acute leukemic transformation. Computed tomography revealed massive splenomegaly measuring 31.9 cm with associated mass effect on adjacent abdominal structures. This case illustrates the long-term clinical course of chronic-phase CML in a young adult with a rare variant Philadelphia chromosome translocation. Despite persistent hematologic abnormalities, marked splenomegaly, and moderate marrow fibrosis nearly a decade after diagnosis, the patient remained in chronic phase without leukemic transformation. The case highlights the importance of comprehensive cytogenetic evaluation, accurate disease-phase assessment, and long-term molecular surveillance in patients with uncommon cytogenetic variants.

Breast cancer often metastasizes to the bone, leading to musculoskeletal symptoms that may mimic benign conditions. Patients with undiagnosed or recurrent malignancies may initially present to first-contact providers, including chiropractors, with non-specific spinal or musculoskeletal pain. Here, we extend the series with two additional cases, highlighting risks of delayed diagnosis, the role of imaging, and chiropractic care. In Case 1, a 62-year-old woman with a history of breast carcinoma presented with progressive left-sided sciatica-like symptoms (pain radiating from the sacroiliac region to the lower extremity), revealing progressive metastases on MRI (e.g., L5 vertebral collapse with retropulsion and severe stenosis) and PET/CT (e.g., new intraspinal extensions at C2, T2, and T4). Multidisciplinary intervention, including radiotherapy, targeted therapy (letrozole, palbociclib, denosumab), and conservative chiropractic management, reduced Visual Analog Scale (VAS) pain scores from 7/10 to 3/10 and improved quality of life from 58/100 to 86/100. In Case 2, a 44-year-old woman presented with constant lumbar pain (7/10 intensity), leading to the discovery of multilevel vertebral collapses (e.g., C7, T3, T5, T8, and L2) and abnormal marrow signals on MRI, confirmed as invasive ductal carcinoma via biopsy and PET/CT. These cases underscore the need for vigilance in patients with an oncologic history presenting with musculoskeletal pain. These clinical outcomes highlight the synergy of an interdisciplinary management model, where primary oncology therapies (radiotherapy and systemic targeted agents) successfully achieve metabolic and structural stabilization of the metastatic lesions, while concurrent, low-force supportive chiropractic care safely focuses on mechanical symptom mitigation and preserving the patient's quality of life.

Cerebrospinal fluid (CSF) otorrhea represents a breach of the temporal bone separating the subarachnoid space from the middle ear and carries a significant risk of meningitis. While most cases are associated with trauma or prior skull base surgery, congenital fistulas may remain occult until unmasked by otologic procedures.  We report the case of a five-year-old male with bilateral profound sensorineural hearing loss and previously unknown labyrinthine anomalies who developed high-flow, pulsatile clear otorrhea during routine left ear myringotomy for recurrent otitis media. Immediate concern for CSF leak prompted fluid collection for beta-2 transferrin analysis and urgent surgical management. Subsequent exploration via lateral temporal bone resection revealed a congenital inner ear fistula with active CSF egress from the vestibule through the oval window. The leak was successfully managed using a multilayer closure technique including vestibular packing with temporalis fascia, cartilage reinforcement, Eustachian tube obliteration, pedicled temporalis muscle flap coverage, and blind sac external auditory canal closure. This case illustrates the recognition and acute intraoperative management of an unanticipated high-flow CSF leak during a routine pediatric otologic procedure, and supports preoperative temporal bone imaging in children with profound sensorineural hearing loss before middle-ear instrumentation. Untreated, such leaks carry a significant risk of life-threatening meningitis.

Designed for tissue engineering and regenerative medicine, silanized polysaccharide-based hydrogels provide stable and biocompatible 3D scaffolds, enabling sol-gel polymerization without the need for toxic chemical reagents. Silanized cellulose derivatives represent a rapidly advancing class of biomaterials that combine the biocompatibility and sustainability of cellulose with the versatile reactivity of organosilanes to create high-performance hydrogels. First developed in 2000 for bone and dental surgery, Si-HPMC is recognized as a self-hardening hydrogel, exhibiting a viscous liquid state at basic pH and a viscoelastic solid state at physiological pH. Since then, numerous studies have investigated Si-HPMC hydrogels, consistently demonstrating their high biocompatibility, strong support for cell viability and proliferation, and functional barrier properties. These features make Si-HPMC a versatile candidate for applications in tissue engineering and regenerative medicine. Furthermore, Si-HPMC-based biocomposites reinforced with nanoparticles, nanofibers, nanotubes, or ceramic particles have emerged as promising matrix hydrogels, combining enhanced mechanical resilience with improved bioactivity, particularly in cartilage, bone, and periodontal tissue engineering. This review highlights the pivotal role of Si-HPMC hydrogels in advancing regenerative medicine, emphasizing their tunable mechanical and biological properties. As next-generation biomaterials, they hold strong potential for applications in dentistry, bone and cartilage repair, intervertebral disc regeneration, and 3D bioprinting.